Cardioprotective Effects of Exercise Training on Doxorubicin-Induced Cardiomyopathy: A Systematic Review With Meta-Analysis of Preclinical Studies

Objective: Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. Methods: : We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Results: : Trained DOX-treated animals improved 7.46% (95%CI 5.58 to 9.34, p<0.001) in FS vs. sedentary animals. Subgroup analyses identified a superior effect of exercise training prior to DOX exposure (MD=8.20, 95%CI 6.27 to 10.13, p=0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was associated with superior effect size in FS (MD=7.13, 95%CI 5.44 to 8.81, p=0.030) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, animal species, gender and cumulative DOX dose did not influence on FS. Conclusions: : Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.